1ol7
From Proteopedia
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|PDB= 1ol7 |SIZE=350|CAPTION= <scene name='initialview01'>1ol7</scene>, resolution 2.75Å | |PDB= 1ol7 |SIZE=350|CAPTION= <scene name='initialview01'>1ol7</scene>, resolution 2.75Å | ||
|SITE= <scene name='pdbsite=AC1:Mg+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Mg+Binding+Site+For+Chain+A'>AC1</scene> | ||
| - | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> | + | |LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5'-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/ | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ol7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ol7 OCA], [http://www.ebi.ac.uk/pdbsum/1ol7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ol7 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Aurora-A is an oncogenic kinase essential for mitotic spindle assembly. It is activated by phosphorylation and by the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. We have uncovered the molecular mechanism of Aurora-A activation by determining crystal structures of its phosphorylated form both with and without a 43 residue long domain of TPX2 that we identified as fully functional for kinase activation and protection from dephosphorylation. In the absence of TPX2, the Aurora-A activation segment is in an inactive conformation, with the crucial phosphothreonine exposed and accessible for deactivation. Binding of TPX2 triggers no global conformational changes in the kinase but pulls on the activation segment, swinging the phosphothreonine into a buried position and locking the active conformation. The recognition between Aurora-A and TPX2 resembles that between the cAPK catalytic core and its flanking regions, suggesting this molecular mechanism may be a recurring theme in kinase regulation. | Aurora-A is an oncogenic kinase essential for mitotic spindle assembly. It is activated by phosphorylation and by the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. We have uncovered the molecular mechanism of Aurora-A activation by determining crystal structures of its phosphorylated form both with and without a 43 residue long domain of TPX2 that we identified as fully functional for kinase activation and protection from dephosphorylation. In the absence of TPX2, the Aurora-A activation segment is in an inactive conformation, with the crucial phosphothreonine exposed and accessible for deactivation. Binding of TPX2 triggers no global conformational changes in the kinase but pulls on the activation segment, swinging the phosphothreonine into a buried position and locking the active conformation. The recognition between Aurora-A and TPX2 resembles that between the cAPK catalytic core and its flanking regions, suggesting this molecular mechanism may be a recurring theme in kinase regulation. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Colon cancer, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603072 603072]] | ||
==About this Structure== | ==About this Structure== | ||
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Structural basis of Aurora-A activation by TPX2 at the mitotic spindle., Bayliss R, Sardon T, Vernos I, Conti E, Mol Cell. 2003 Oct;12(4):851-62. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14580337 14580337] | Structural basis of Aurora-A activation by TPX2 at the mitotic spindle., Bayliss R, Sardon T, Vernos I, Conti E, Mol Cell. 2003 Oct;12(4):851-62. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14580337 14580337] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| + | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Transferred entry: 2 7.11 1]] | ||
[[Category: Bayliss, R.]] | [[Category: Bayliss, R.]] | ||
[[Category: Conti, E.]] | [[Category: Conti, E.]] | ||
| - | [[Category: ADP]] | ||
| - | [[Category: MG]] | ||
[[Category: atp-binding]] | [[Category: atp-binding]] | ||
[[Category: cell cycle]] | [[Category: cell cycle]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:47:04 2008'' |
Revision as of 19:47, 30 March 2008
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| , resolution 2.75Å | |||||||
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| Sites: | |||||||
| Ligands: | , , | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE OF HUMAN AURORA-A 122-403 PHOSPHORYLATED ON THR287, THR288
Overview
Aurora-A is an oncogenic kinase essential for mitotic spindle assembly. It is activated by phosphorylation and by the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. We have uncovered the molecular mechanism of Aurora-A activation by determining crystal structures of its phosphorylated form both with and without a 43 residue long domain of TPX2 that we identified as fully functional for kinase activation and protection from dephosphorylation. In the absence of TPX2, the Aurora-A activation segment is in an inactive conformation, with the crucial phosphothreonine exposed and accessible for deactivation. Binding of TPX2 triggers no global conformational changes in the kinase but pulls on the activation segment, swinging the phosphothreonine into a buried position and locking the active conformation. The recognition between Aurora-A and TPX2 resembles that between the cAPK catalytic core and its flanking regions, suggesting this molecular mechanism may be a recurring theme in kinase regulation.
About this Structure
1OL7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis of Aurora-A activation by TPX2 at the mitotic spindle., Bayliss R, Sardon T, Vernos I, Conti E, Mol Cell. 2003 Oct;12(4):851-62. PMID:14580337
Page seeded by OCA on Sun Mar 30 22:47:04 2008
